This Observational protocol will attempt to verify two recent and very critical concepts in ALZ Clinical Research by studying high-risk individuals who already are taking medications which may prevent the onset of ALZ.

• It may be possible to determine the future development of ALZ in a preclinical state in a cognitively normal but high risk individual at least 18-24 months before any symptoms develop of cognitive impairment.
• Early treatment of these cognitively normal high-risk persons with subclinical pre-ALZ can prevent of delay the occurrence and severity of ALZ.

Caveats

Neither this protocol nor the fMRI imaging are designed or intended to diagnose or treat ALZ, nor develop or use medications or diagnostic neuroimaging outside of already approved and accepted parameters. Persons who volunteer to be study subjects in this observational protocol will be under the care of their primary care / specialty physician, who will order tests and treatments as they see appropriate.

Although there is a very large body of peer-reviewed scientific literature demonstrating that certain functional MRI patterns are associated with certain neurologic conditions, the utilization of fMRI for the evaluation of neurologic disorders is still considered an emerging science and therefore in the investigational stage. Although this protocol will report on brain patterns of certain neurologic conditions such as cognitive impairment and Alzheimer's disease, based on patterns published in peer-reviewed journals, such findings are not considered stand alone or diagnostic per se and should always be considered by the PMD in conjunction with the patient's clinical condition. These data should only be used as additional information to add to the PMD's diagnostic impression.

Prospective observational study participants age 50-75 years are identified who are currently (<1 month) taking or will soon (within 3 months) start taking study medications of interest thru their own physician.

Prospective observational study participants are explained how persons can be cognitively normal but at high risk for developing clinical ALZ, and that this risk can be prospectively identified.

They are advised that there is some rationale that medications they are or will soon be taking may have a protective effect in delaying the onset of ALZ, and that protective effect can be monitored.

They are asked if they would like to participate in a protocol that monitors their prospective risk for developing ALZ short term, and whether certain of their prescribed medications may have a protective effect. Those who are accepting to be participants are then enrolled in the study.

Enrollees are tested for risk factors for having pre-clinical ALZ. Individuals identified as being at risk at baseline are followed at 6 month intervals for a 24 month period using psychometric testing and functional neuroimaging. Their maintenance of cognitive stability or cognitive decline is monitored while under the care of their PMD and while taking medications of interest.

Inclusion Criteria:

• 50 to 75 years old,
• Normal baseline cognitive function by standard psychometric testing.
• Able to privately fund psychometric and neuroimaging studies if not covered by their insurance,
• Able to give written Informed Consent,
• Ascent for collaboration by their primary care or specialty physician,
• Currently taking (<1 month) or planning to take (within the next 3 months) medications which are identified in the study group of interest, prescribed by and under the care of a PMD or specialty physician.

Exclusion Criteria:

• Inability to undergo MR Imaging : Claustrophobia, certain metal implants,

Adults at high risk of developing ALZ within 18-48 months but are currently cognitively normal for their age sex matching group. Risk factors include parents with a history of ALZ, and/or positive APOE4 alleles.